STTR Phase I: Development of a novel system to manufacture therapies inside the human body

这个小企业技术转让（STTR）第一阶段项目的更广泛的影响是通过开发一个系统来直接在患者中合成急需的药物疗法来改善药物输送。如果成功，这一进步将减少对复杂和昂贵的制造的需求，消除对冷藏药物运输和储存的依赖，并消除对重复注射的需求。开发这样一个系统将可适用于人类健康和疾病的不同应用，将能抵御流行病或自然灾害造成的供应链中断，并将导致向地球仪各地不同的患者群体公平提供药物。 拟议的项目旨在开发一种能够支持生物药物直接在体内输送的动态活体药物。在过去的十年中，已经进行了许多尝试，使用工程细菌和病毒作为活体药物安全有效地向人类提供生物制剂。 目前的系统充满了问题，主要源于这些载体的免疫原性。这一关键的技术和创新差距-在体内安全地长时间直接生产生物制剂-可以通过基因工程无毒生物体共生体来表达感兴趣的蛋白质来实现。在这项研究中，血液共生体将被基因工程改造以表达β-葡萄糖脑苷脂酶或胰岛素，目的是分别产生治疗戈谢病和糖尿病的活药物。将在体外和体内评估工程化合物的分泌、活性和耐久性。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的知识价值和更广泛的影响审查标准进行评估。

The broader impact of this Small Business Technology Transfer (STTR) Phase I project is to improve drug delivery by developing a system to synthesize much needed drug therapies directly in patients. This advancement, if successful, would reduce the need for complex and expensive manufacturing, eliminate the reliance on refrigerated drug shipment and storage, and remove need for repeated injections. Development of such a system would be adaptable for different applications across human health and disease, would be resistant to supply chain disruptions caused by pandemics or natural disasters, and would result in the equitable delivery of medications to diverse patient populations across the globe. The proposed project seeks to develop a dynamic living medicine capable of supporting the delivery of biological drugs directly in vivo. Over the last decade, many attempts have been made to deliver biologics safely and efficiently to humans using engineered bacteria and viruses as living medicines. The current system is fraught with problems, mostly stemming from the immunogenicity of these vectors. This critical technological and innovation gap - the manufacture biologics directly in vivo safely for extended periods of time - may be achieved through the genetic engineering of avirulent organism symbionts to express proteins of interest. In this study, blood symbionts will be genetically engineered to expresses either β-glucocerebrosidase or insulin, with the goal of generating living medicines to treat Gaucher’s disease and diabetes, respectively. The secretion, activity, and durability of the engineered compounds will be assessed in vitro and in vivo. The safety and efficacy of this therapeutic approach will be assessed in pre-clinical models.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.